The Usefulness of Ultrasonography for Supporting the Differentiation, Diagnosis, and Treatment of Atypical Fibroxanthoma and Pleomorphic Dermal Sarcoma.

Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are rare histomorphological variants of a disease spectrum. After ruling out other tumor entities by immunohistochemistry, PDS can be differentiated from AFX by infiltration into the subcutis, while AFX remains confined to the dermis. The therapeutic approach is more aggressive in PDS as it can potentially metastasize. We assessed the usefulness of preoperative sonography in differentiating between the two tumor entities by identifying a potential subcutaneous infiltration. In our patients (n = 13), preoperative sonography identified and differentiated AFX and PDS with 100% accuracy and even changed the initial histological suspicion of AFX to PDS in 3 cases (23%), which was confirmed after tumor resection. Preoperative sonography of these tumors could strengthen the clinical diagnosis, avoid a delay in therapy initiation and improve patient counseling. While for AFX, micrographic-controlled surgery suffices, for PDS, resection with 2 cm safety margins and lymph node sonography to rule out lymphonodal involvement is necessary. Hence, ultrasonography can improve clinical practice by providing helpful information for dermatosurgeons, which cannot be obtained during clinical examination.

Rationale for Using High-Frequency Ultrasound as a Routine Examination in Skin Cancer Surgery: A Practical Approach.

Ultrasound and high-frequency ultrasound assessment of melanoma and non-melanoma skin cancer in the pre-therapeutical setting is becoming increasingly popular in the field of dermatosurgery and dermatooncology, as it can provide clinicians with relevant, "in vivo" parameters regarding tumor lateral and depth extension as well as potential locoregional spread, cancelling the need of more extensive imaging methods and avoiding a delay in diagnosis. Furthermore, preoperative sonography and color Doppler can aid in orienting the clinical diagnosis, being able in numerous situations to differentiate between benign and malignant lesions, which require a different therapeutic approach. This preoperative knowledge is of paramount importance for planning an individualized treatment regimen. Using sonography at the time of diagnosis, important surgical complications, such as neurovascular damage, can be avoided by performing a preoperative neurovascular mapping. Furthermore, sonography can help reduce the number of surgical steps by identifying the lesions' extent prior to surgery, but it can also spare unnecessary surgical interventions in cases of locally advanced lesions, which infiltrate the bone or already present with locoregional metastases, which usually require modern radiooncological therapies in accordance to European guidelines. With this review, we intend to summarize the current indications of sonography in the field of skin cancer surgery, which can help us improve the therapeutic attitude toward our patients and enhance patient counseling. In the era of modern systemic radiooncological therapies, sonography can help better select patients who qualify for surgical procedures or require systemic treatments due to tumoral extension.

Pre-operative high-frequency ultrasound: a reliable management tool in auricular and nasal non-melanoma skin cancer.

BACKGROUND AND OBJECTIVES: The knowledge of depth infiltration in non-melanoma skin cancer (NMSC) using pre-operative ultrasound could enable clinicians to choose the most adequate therapeutic approach, avoiding unnecessary surgeries and expensive imaging methods, delaying diagnosis and treatment. Our single-center retrospective study determined the usefulness of high-frequency ultrasound (HFUS) for depth infiltration assessment in auricular and nasal NMSC and assessed the subsequent change in therapeutic approach. PATIENTS AND METHODS: In 60 NMSC cases, we assessed the accuracy of HFUS in cartilaginous/bone infiltration detection as well as the correlation of sonographic and histological parameters. RESULTS: In 16.6% of cases, a deep cartilaginous/bone involvement or locoregional disease was identified pre-operatively, resulting in a changed therapeutical scheme of radio-immunological treatment rather than surgery. In two cases, pre-operative HFUS identified local cartilage infiltration, reducing the number of surgical procedures. Forty-eight remaining lesions with no depth infiltration were excised; a correlation of > 99% between the histologic and sonographic tumor depth (p<0.001) was found. CONCLUSIONS: Pre-surgical HFUS influences the therapeutic management in NMSC by detecting subclinical involvement of deeper structures, avoiding more extensive diagnostics, reducing costs, and improving healthcare quality. High-frequency ultrasound should be implemented in dermatosurgery before tumor excision for optimized therapy and improved patient counseling.

[Skin aging-cellular senescence : What is the future?] / Hautalterung ­ zelluläre Seneszenz : Wohin geht die Reise?

BACKGROUND: Cellular senescence is the main cause of skin and organ aging and is associated with a wide range of aging-related diseases. OBJECTIVES: To understand which senolytics, senomorphics, and cell-based therapies have been developed to alleviate and even rejuvenate skin aging and reduce cellular senescence. METHODS: Basic literature for the mode of action of senolytics and senomorphics and their clinical perspectives in daily routine are discussed. RESULTS: Various causes lead to mitochondrial dysfunction and the activation of pro-aging signaling pathways, which eventually lead to cellular senescence with degradation of structural proteins of the dermal connective tissue and severe suppression of regenerative stem cell niches of the skin. CONCLUSIONS: Depletion of senescent cells suppress skin aging and enforce rejuvenation of skin and other organs and their function. The removal of senescent cells by cells of the native immune system is severely disturbed during aging. Selected senolytics and senomorphics are approved and are already on the market.

Ultrasound Assessment of Skin Tumors Local Recurrence.

Skin cancer may recur at or around the surgical site despite wide excisions. Prompt clinical and sonographic detection of local recurrence is important since subjects with relapsing melanomas or nonmelanoma malignancies can be managed efficaciously, with a relevant impact on morbidity and survival. Ultrasound is being employed with increasing frequency in the assessment of skin tumors, but most of the published articles relate to initial pretherapeutic diagnosis and staging. This review aims to offer an illustrated guide to the sonographic evaluation of locally recurring skin cancer. We introduce the topic, then we provide some sonographic tips for patient follow-up, then we describe the ultrasound findings in case of local recurrence, illustrating the main mimickers, and finally, we mention the role of ultrasound in guiding diagnostic and therapeutic percutaneous procedures.

Ultrasonographic Assessment of Depth Infiltration in Melanoma and Non-melanoma Skin Cancer.

The preoperative assessment of infiltration depth in melanoma and non-melanoma skin cancer by means of high-frequency ultrasound (≥18 MhZ) is essential for optimizing the therapeutic approach in our patients. Often, histologically confirmed skin tumors are directly referred to surgical departments for resection, and sonography is increasingly helping us identify those subjects who are no longer candidates for extensive surgical interventions. In cases of deep tumor infiltration, with potential surgical failure e.g. impairment of the quality of life and significant esthetic and functional complications, preoperative sonography can guide the surgeon to withstand from an operation and decide instead in favor of less mutilating radiooncological or medical treatment options. Furthermore, in melanoma patients, the preoperative knowledge of the tumor depth is essential for the determination of the therapeutic approach, the correct safety margins and the need of a sentinelnode biopsy. We herein encourage the use of preoperative sonography in dermatologic surgery whenever possible as it represents an easy, painless, "in vivo" method, which provides clinicians with significant clinical information that can influence the therapy and improve patient compliance.

Dermatological assessment of thick-skinned patients before rhinoplasty-what may surgeons ask for?

Rhinoplasty is considered a very challenging surgery since minimal changes of this central area of the face may significantly impact a person's appearance and self-awareness. This is even more challenging in thick-skinned patients because results are less predictable, and changes to the osseocartilaginous framework (OCF) may not be sufficiently visible due to the blanket effect of the thick skin. Furthermore, pre-existing skin conditions may exacerbate following surgery. Therefore, managing patients with extremely thick skin or patients who suffer from pre-existing dermatological conditions such as rosacea or acne requires a synergy of surgeons and dermatologists to achieve optimal results. In this article, we review the most significant pre- and post-surgical regimens that surgeons and dermatologists should apply in selected patients to achieve optimal results after rhinoplasty.

Short-Interval, Low-Dose Peptide Receptor Radionuclide Therapy in Combination with PD-1 Checkpoint Immunotherapy Induces Remission in Immunocompromised Patients with Metastatic Merkel Cell Carcinoma.

Merkel cell carcinoma (MCC) is a neuroendocrine skin cancer of the elderly, with high metastatic potential and poor prognosis. In particular, the primary resistance to immune checkpoint inhibitors (ICI) in metastatic (m)MCC patients represents a challenge not yet met by any efficient treatment modality. Herein, we describe a novel therapeutic concept with short-interval, low-dose 177Lutetium (Lu)-high affinity (HA)-DOTATATE [177Lu]Lu-HA-DOTATATE peptide receptor radionuclide therapy (SILD-PRRT) in combination with PD-1 ICI to induce remission in patients with ICI-resistant mMCC. We report on the initial refractory response of two immunocompromised mMCC patients to the PD-L1 inhibitor avelumab. After confirming the expression of somatostatin receptors (SSTR) on tumor cells by [68Ga]Ga-HA-DOTATATE-PET/CT (PET/CT), we employed low-dose PRRT (up to six treatments, mean activity 3.5 GBq per cycle) at 3-6 weeks intervals in combination with the PD-1 inhibitor pembrolizumab to restore responsiveness to ICI. This combination enabled the synergistic application of PD-1 checkpoint immunotherapy with low-dose PRRT at more frequent intervals, and was very well tolerated by both patients. PET/CTs demonstrated remarkable responses at all metastatic sites (lymph nodes, distant skin, and bones), which were maintained for 3.6 and 4.8 months, respectively. Both patients eventually succumbed with progressive disease after 7.7 and 8 months, respectively, from the start of treatment with SILD-PRRT and pembrolizumab. We demonstrate that SILD-PRRT in combination with pembrolizumab is safe and well-tolerated, even in elderly, immunocompromised mMCC patients. The restoration of clinical responses in ICI-refractory patients as proposed here could potentially be used not only for patients with mMCC, but many other cancer types currently treated with PD-1/PD-L1 inhibitors.

Ultrasonography in dermatologic surgery: revealing the unseen for improved surgical planning.

Ultrasonography (US) is a modern, in vivo imaging method, which is increasingly being used in dermatology as a complementary tool to clinical examination and dermoscopy. At higher frequencies (15 MHz and above), US is an established method for assessing benign and malignant skin lesions, locoregional staging, monitoring the therapeutic efficacy in various inflammatory skin conditions, and patient follow-up. One field, which may increasingly benefit from performant imaging techniques such as US is dermatologic surgery. Preoperative imaging of cutaneous tumors, inflammatory skin conditions (hidradenitis suppurativa, abscesses, etc.), or nail pathology provide dermatologic surgeons with relevant information for an optimal surgical planning, identifying potential complex aspects which might require interdisciplinary approaches, herein sparing unnecessary surgical interventions and increasing patients' compliance. In this review, we discuss the increasing significance of US in the field of dermatologic surgery, as well as the spectrum of cutaneous pathology where sonography can aid in the preoperative setting to provide a more precise, individualized surgical planning for better counseling to our patients and improved surgical results.

European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Position Statement on Dermatologic Ultrasound.

Dermatologic ultrasound is a recent application of ultrasound for the evaluation of healthy skin and appendages and their diseases. Although the scientific literature regarding this application is still not sufficient for evidence-based guidelines, general recommendations issued by scientific societies are necessary. The EFSUMB (European Federation of Societies for Ultrasound in Medicine and Biology) steering committee for dermatologic ultrasound has developed a series of consensus position statements regarding the main fields of dermatologic ultrasound (technical requirement, normal skin and appendages, inflammatory skin diseases, tumoral skin diseases, aesthetic dermatology and practice-training requirements). This document is the foundation for future evidence-based recommendations and guidelines for dermatologic ultrasound practice.